Wet ethanol is a biofuel that can be rapidly integrated into the existing transportation sector infrastructure and have an immediate impact on decarbonization. Compared to conventional hydrocarbon fuels, wet ethanol has unique fuel properties (e.g., short carbon chain, oxygenated, high heat of vaporization, no cool-flame reactivity), which can actually improve the efficiency and engine-out emissions of internal combustion engines while decarbonizing. In this work, wet ethanol 80 (80% ethanol, 20% water by mass) was experimentally studied at high loads under boosted conditions in compression ignition to study the tradeoffs in efficiency and emissions based on boosting and injection strategies. Specifically, this work explores the potential of adding a third, mixing-controlled injection at high loads. The results indicate that adding a third, mixing-controlled injection results in combustion stabilization at high loads, where the peak pressure limit of the engine is a constraint that requires combustion phasing to retard. However, since the heat of vaporization of wet ethanol 80 is ~6% of its lower heating value, evaporation of fuel injected near top dead center imposes a thermodynamic efficiency penalty by absorbing heat from the working fluid at a time in the cycle when adding heat produces net work out. Additionally, the mixing-controlled injection increases NOx emissions. Therefore, the amount of fuel injected in the mixing-controlled injection should be limited to only what is necessary to stabilize combustion. Ultimately, by using wet ethanol 80 in a triple injection strategy, a load of 22 bar IMEPn is achieved with a net fuel conversion efficiency of 42.2%, an engine-out indicated specific emissions of NOx of 1.3 g/kWh, and no measurable particulate matter, while maintaining a peak cylinder pressure below 150 bar.